The objectives of this research proposal are to investigate the roles of Ca and Na ions in the electrophysiological and mechanical functions of heart muscle cells. This research proposal has a two fold task. First, it attempts to provide new insights into Na and Ca ion transport mechanisms across cell membrane: Na-Ca exchange system. Second, it is to study the roles of Ca and Na ions in the regulation of contractile force of heart muscle: positive ionotropic effects which are clinically important. To achieve these tasks, intracellular free Ca ion concentration ((Ca)i), intracellular Na ion activity ((Na)i) and contractile tension (T) will be measured simultaneously in the following conditions. (1) Effects of external cations on (Ca)i, (Na)i and T. a) Reduction of (Na)o from 153 mM (normal) to 75, 20 and 0 mM. b) Changes of (Ca)o from 1.8 mM (normal) to 9.0 and 0.36 mM. c) The changes of (Ca)o and (Na)o in the presence of Mn2 (known to inhibit Ca ions transport). d) Changes of (Ca)o and (Na)o with the ratio, (Ca)o/(Na)o2 constant. e) Changes of (K)o from 5.4 mM (normal) to 50 and 100 mM (contracture solutions) and to 1 mM (inhibition of Na pump). (2) Effects of cardiac glycoside, strophanthidin at the concentrations of 10 to the minus 8th power, 5 times 10 to the minus 8th power, 10 to the minus 7th power, 5 times 10 to the minus 7th power, 10 to the minus 6th power, 5 times 10 to the minus 6th power and 10 to the minus 5th power M on (Ca)i, (Na)i and T. (3) Effects of monovalent cation ionophores, monensin and nigericin at the concentrations from 5 micron M to 40 micron M on (Ca)i, (Na)i and T. Intracellular free Ca ion concentration and intracellular Na ion activity will be measured directly and continuously with Ca ions-selective microelectrodes and Na ion-selective microelectrodes respectively. At the same time, contractile tension will be measured with a photoelectric transducer.